The mechanism of action of three classes of antitumor drugs will be assessed in human tumor cells in tissue culture, and will include studies of ribosomal RNA processing, transcription, methylation of RNA and DNA and protein phosphorylation. The first project deals with nucleoside antimetabolites as exemplified by the pyrrolopyrimidines tubercidin, toyocamycin and sangivamycin, the carbocylic cycopentene analog of adenosine, neplanocin-A, and the pyrimidines arabinosyl-5-azacytosine, 2'-deoxyazacytidine, azacytidine, and 5-fluorouridine. The second study involves examining the cytocidal activity of human immune interferon both alone and in combination with double-stranded RNA, and analogs of the interferon-induced 2', 5'-oligoadenylates as prototypes of a new class of antitumor drugs. Chemically modified 2',5'-oligoadenylates will be studied for their ability to activate latent endoribonuclease and inhibit 2',5'-oligo-(A) phosphodiesterase.